- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03532087
Study to Identify the Impact of Denosumab on the Immune System in Patients With HER2 Negative Breast Cancer (PERIDENO)
January 16, 2020 updated by: Borstkanker Onderzoek Groep
Explorative Trial to Identify the Impact of Denosumab on the Systemic Immunity and Local Immunologic Microenvironment in Postmenopausal Patients With HER2 Negative Breast Cancer
The aim of this prospective, randomized, multicenter, open-label, explorative phase II study is to identify the impact of (neo)adjuvant denosumab on the systemic immunity and local immunologic microenvironment in postmenopausal patients with HER2 negative non-metastatic primary breast cancer.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Detailed Description
In this study, postmenopausal patients with stage T1c + grade 3, stage II or III, HER2-negative breast cancer, which are planned to undergo surgery followed by adjuvant AC-T chemotherapy, are randomized between no denosumab, denosumab low dosing and denosumab high dosing.
Denosumab administration will start one week before surgery and continue until the last chemotherapy cycle.
Study Type
Interventional
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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-
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Almelo, Netherlands
- Ziekenhuisgroep Twente (Twenteborg ZH Almelo)
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Apeldoorn, Netherlands
- Gelre Ziekenhuizen
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Heerlen, Netherlands
- Zuyderland Medisch Centrum (Heerlen)
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Hoofddorp, Netherlands
- Spaarne Gasthuis (Hoofddorp)
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Leiden, Netherlands
- Leiden University Medical Center
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Schiedam, Netherlands
- Fransiscus (Vlietland)
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Venlo, Netherlands
- VieCuri Medisch Centrum (Venlo)
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Zoetermeer, Netherlands
- 't Lange Land Ziekenhuis
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Postmenopausal, defined as 1 year without menstrual activity, previous bilateral oophorectomy, age older than 60 years or baseline FSH >20 U/l and estradiol <110 pmol/l.
- Clinical stage T1c + grade 3, stage II or III breast cancer amenable to adjuvant AC-T combination chemotherapy.
- Measurable disease (breast and/or lymph nodes).
- Histological proven HER2-negative breast cancer in the core biopsy material.
- WHO 0-2.
- Adequate bone marrow function (within 4 weeks prior to randomization): WBC≥3.0x109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l.
- Adequate liver function (within 4 weeks prior to randomization): bilirubin ≤1.5 X upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL.
- Adequate renal function (within 4 weeks prior to randomization): the calculated creatinine clearance should be ≥50 ml/min.
- Albumin-adjusted serum calcium > 2.0 mmol/L (8.0mg/dL)
- Accessible for treatment and follow-up.
- Written informed consent.
Exclusion Criteria:
- Evidence of distant metastases (M1).
- History of breast cancer.
- Prior chemotherapy or radiation therapy.
- Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
- Prior or current bisphosphonate or denosumab usage.
- Serious other diseases as recent (last 6 months) myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias.
- Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible), non-healed dental or oral surgery, a current or prior diagnosis of osteonecrosis of the jaw or planned invasive dental procedures for the course of the study.
- Known hypersensitivity reaction to any of the components of the treatment.
- Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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No Intervention: No denosumab
All patients undergo surgery followed by adjuvant chemotherapy.
Patients in this study arm are not additionally treated with denosumab.
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Experimental: Denosumab 120 mg
All patients undergo surgery followed by adjuvant chemotherapy.
Patients in this study arm are additionally treated with denosumab 120 mg every 3 weeks.
First denosumab gift is before surgery, last denosumab gift is together with the last cycle of chemotherapy.
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Denosumab 120 mg every 3 weeks.
Other Names:
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Experimental: Denosumab 60 mg
All patients undergo surgery followed by adjuvant chemotherapy.
Patients in this study arm are additionally treated with denosumab 60 mg every 6 months.
First denosumab gift is before surgery, last denosumab gift is together with the last cycle of chemotherapy.
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Denosumab 60 mg every 6 months.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in intratumoral T-cell (CD4, CD8 and Treg) numbers and function between the baseline biopsy and the surgical specimen.
Time Frame: The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment.
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The change will be determined by use of IHC and immunofluorescent stainings.
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The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment.
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Change in myeloid cell (M1/M2 Macrophage, MDSC, DC) numbers and function between the baseline biopsy and the surgical specimen.
Time Frame: The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment.
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The change will be determined by use of IHC and immunofluorescent stainings.
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The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Shift in activated T effector cell levels.
Time Frame: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Shifts will be determined by comparing PBMCs (using flow cytometry) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.
|
Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
|
Shift in regulatory T-cell levels.
Time Frame: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
|
Shifts will be determined by comparing PBMCs (using flow cytometry) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.
|
Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Change in functional response of T-cells.
Time Frame: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Changes will be determined by comparing PBMCs (using stimulation tests) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.
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Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Change in mature and immature myeloid cells (M1/M2 macrophage, MDSC, DC).
Time Frame: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
|
Shifts will be determined by comparing PBMCs (using flow cytometry) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.
|
Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Shift in myeloid cell function.
Time Frame: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
|
Shifts will be determined by comparing PBMCs (using triggering tests) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.
|
Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
|
Change in stimulation capacity APCs.
Time Frame: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
|
Changes will be determined by comparing PBMCs (using restimulation tests) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.
|
Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Change in serum levels of RANKL and OPG.
Time Frame: Measurements will be done in serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Changes will be determined by comparing serum before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration, using ELISA.
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Measurements will be done in serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Change in serum cytokine levels (TNF-alpha, interleukines, IFN gamma).
Time Frame: Measurements will be done in serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Changes will be determined by comparing serum before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration, using luminex.
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Measurements will be done in serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.
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Correlation of tumor measurements with serum measurements.
Time Frame: Measurements will be done in tumor material and serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.
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Measurements in tumor and serum will be correlated.
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Measurements will be done in tumor material and serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.
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Correlation of tumor measurements with PBMCs measurements.
Time Frame: Measurements will be done in tumor material and PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.
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Measurements in tumor and PBMCs will be correlated.
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Measurements will be done in tumor material and PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.
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Correlation of serum measurements and PBMCs measurements.
Time Frame: Measurements will be done in PBMCs/serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.
|
Measurements in serum and PBMCs will be correlated.
|
Measurements will be done in PBMCs/serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.
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Toxicity according to NCI CTCAE v4.03.
Time Frame: Toxicity will be assessed from start treatment up to 30 days following the last dose of treatment.
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Toxicities are graded according to NCI CTCAE v4.03.
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Toxicity will be assessed from start treatment up to 30 days following the last dose of treatment.
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Difference in descriptive event free survival (EFS) at 3 years based on immune response.
Time Frame: EFS will be determined after 3 years.
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After 3 years of follow up, differences in EFS based on immune response will be determined.
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EFS will be determined after 3 years.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Judith R Kroep, MD PhD, Leiden University Medical Center
- Principal Investigator: Gerrit-Jan Liefers, MD PhD, Leiden University Medical Center
- Principal Investigator: Sjoerd H van der Burg, Prof. Dr., Leiden University Medical Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
February 1, 2018
Primary Completion (Anticipated)
February 1, 2021
Study Completion (Anticipated)
June 1, 2023
Study Registration Dates
First Submitted
February 5, 2018
First Submitted That Met QC Criteria
May 9, 2018
First Posted (Actual)
May 22, 2018
Study Record Updates
Last Update Posted (Actual)
January 18, 2020
Last Update Submitted That Met QC Criteria
January 16, 2020
Last Verified
July 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- BOOG-2017-02
- 2016-005210-22 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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